Revised Framingham Stroke Risk Profile: Association with Cognitive Status and MRI-Derived Volumetric Measures

Background: The Framingham Stroke Risk Profile (FSRP) was created in 1991 to estimate 10-year risk of stroke. It was revised in 2017 (rFSRP) to reflect the modern data on vascular risk factors and stroke risk. Objective: This study examined the association between the rFSRP and cognitive and brain aging outcomes among participants from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS). Methods: Cross-sectional rFSRP was computed at baseline for 19,309 participants (mean age = 72.84, SD = 8.48) from the NACC-UDS [9,697 (50.2%) normal cognition, 4,705 (24.4%) MCI, 4,907 (25.4%) dementia]. Multivariable linear, logistic, or ordinal regressions examined the association between the rFSRP and diagnostic status, neuropsychological test performance, CDR (R) Sum of Boxes, as well as total brain volume (TBV), hippocampal volume (HCV), and log-transformed white matter hyperintensities (WMH) for an MRI subset (n= 1,196). Models controlled for age, sex, education, racial identity, APOE epsilon 4 status, and estimated intracranial volume for MRI models. Results: The mean rFSRP probability was 10.42% (min = 0.50%, max =95.71%). Higher rFSRP scores corresponded to greater CDR Sum of Boxes (beta = 0.02, p = 0.028) and worse performance on: Trail Making Test A (beta = 0.05, p < 0.001) and B (beta=0.057, p <0.001), and Digit Symbol (beta = -0.058, p <0.001). Higher rFSRP scores were associated with increased odds for a greater volume of log-transformed WMH (OR = 1.02 per quartile, p= 0.015). No associations were observed for diagnosis, episodic memory or language test scores, HCV, or TBV. Conclusion: These results support the rFSRP as a useful metric to facilitate clinical research on the associations between cerebrovascular disease and cognitive and brain aging.